Prevention of Ovarian Cancer in Women Participating in Mammography Abstract: The evidence-based policy that we seek to promote is risk-reducing salpingo-oophorectomy (RRSO) in women at high risk (HR) for ovarian cancer. Impediments to the successful translation of this policy are that some women are not aware of their risk, and that the appropriate timing of the surgery remains unclear. Our strategy to enhance widespread adoption and institutionalization of this policy is to take advantage of the availability of family history (FH) data in mammography systems in order to systematically identify HR women for referral to risk/genetic counseling (R/GC). In addition we will explore the use of serum markers as risk prediction tools to complement FH. Our long-term goal is prevention of ovarian cancer. An intervention has been demonstrated to work well: prophylactic removal of the ovaries and fallopian tubes once child-bearing is completed. While it would be inappropriate to recommend this surgery for all women, it is recommended for women with a strong FH suggestive of an inherited susceptibility, especially for those with a documented mutation in BRCA1 or BRCA2. The first impediment, that there is no systematic identification of HR women, can be addressed using available data and systems. The additional impediments, that most ovarian cancer occurs in women without a mutation or FH and that the timing of RRSO in these women is uncertain, require a novel approach. We will explore the use of serum markers to predict diagnosis of ovarian cancer in the HR population. We will identify women at HR based on FH at the time of their annual mammogram for referral to a genetic counselor (GC). A randomized controlled trial (RCT) will be performed at the Swedish Breast Cancer Center (SBCC) to evaluate the efficacy of this strategy in increasing rates of RRSO. An effectiveness study of the same strategy will be conducted at Group Health (GH) of Puget Sound to learn how guidelines for receipt of R/GC are adopted in practice. In addition we will explore the novel use of risk prediction serum markers to predict the diagnosis of malignancy or pre-invasive cancer in HR women enrolled in the study. This work will provide the evidence needed to optimize strategies for widespread adoption and institutionalization of systematic identification of HR women for appropriate intervention to prevent ovarian cancer incidence and mortality. Keywords: ovarian cancer, prevention, prophylactic surgery, risk, biomarkers, screening, symptoms STATEMENT We will evaluate a system-wide strategy to routinely identify women with a significant family history of breast and ovarian cancer, so that they can be informed by genetic counselors of their high risk for these cancers. Our goal is to promote surgical removal of ovaries and fallopian tubes in women who are at very high risk for these cancers, because there is clear evidence that this surgery can reduce the risk for ovarian cancer by over 90%, as well as the risk of breast cancer by 50% if the procedure is performed prior to menopause. A novel aspect of our work is that we will also evaluate a panel of serum markers for its ability to predict ovarian malignancy within the next two years, to assist high-risk women in their decision-making about the timing of preventive actions.